The occurrence of a first full term pregnancy at an early age in women profoundly decreases the risk of breast cancer compared to women have having been pregnant or women having a first full term pregnancy at age 35 or older. Parous rats and mice are also nearly completely resistant to mammary carcinogenesis induced by chemical carcinogenesis. During the last several years, we have made considerable progress in understanding the biological basis of parity-induced refractoriness to mammary carcinogenesis in rats and mice. The major interest of this proposal is to investigate the nature of parity-induced refractoriness at the molecular level by expanding our ongoing studies using the rat experimental model. Our objective is divided into two parts. First, we wish to investigate differential gene expression between mammary glands that are either susceptible (virgin) or refractory (parous or exogenous hormone treated) to mammary carcinogenesis. Second, we would like to undertake a detailed characterization and analysis of two genes differentially exposed in susceptible versus refractory rats. It is our belief that parity and exogenous hormonal treatment induce refractoriness to, or protection from mammary carcinogenesis by similar mechanisms. The ultimate goal of these studies is to generate an experimental paradigm that an be used to develop strategies for the prevention of human breast cancer without adverse effects on their health and quality of life.